Evidence map›Paper›PMID 26883712›Full record

ArticleAntimicrobial agents and chemotherapy2016

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon.

Lukas Mechler, Eve-Julie Bonetti, Sebastian Reichert, Matthias Flötenmeyer, Jacques Schrenzel, Ralph Bertram, Patrice François, Friedrich Götz

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 38 citations in OpenAlex.

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  12. Adaptive laboratory evolution and independent component analysis disentangle complex vancomycin adaptation trajectories.Proceedings of the National Academy of Sciences of the United States of America · 2022
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  13. Review
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  16. Lytic bacteriophages facilitate antibiotic sensitization ofAntimicrobial agents and chemotherapy · 2021
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  17. Bacterial Targets of Antibiotics in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

Lukas MechlerMicrobial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tübingen, Germany.
Eve-Julie BonettiGenomic Research Laboratory, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Sebastian ReichertMicrobial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tübingen, Germany.
Matthias FlötenmeyerMax Planck Institute for Developmental Biology, Tübingen, Germany.
Jacques SchrenzelGenomic Research Laboratory, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Ralph BertramMicrobial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tübingen, Germany Research Office, Paracelsus Medical University, Nürnberg, Germany.
Patrice FrançoisGenomic Research Laboratory, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Friedrich GötzMicrobial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tübingen, Germany friedrich.goetz@uni-tuebingen.de.
University of Tübingen · DEUniversity Hospital of Geneva · CHMax Planck Institute for Developmental Biology · DEParacelsus Medizinische Privatuniversität · DEUniversity of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding the mechanisms of how bacteria become tolerant toward antibiotics during clinical therapy is a very important object. In a previous study, we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in the pitA6 mutant differs from classical resistance mechanisms since there is no increase in the MIC. In this follow-up study, we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that 234 genes were at least 2.0-fold differentially expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism, and replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt operon, which is induced by the accumulation of intracellular Pi The GraXRS system, known as an activator of the dlt operon (d-alanylation of teichoic acids) and of the mprF gene (multiple peptide resistance factor), is not involved in DAP tolerance of the pitA6 mutant. In conclusion, DAP tolerance of the pitA6 mutant is due to an upregulation of the dlt operon, triggered directly or indirectly by the accumulation of Pi.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsDaptomycinMicrobial Sensitivity TestsOperonPoint MutationStaphylococcus aureusTeichoic AcidsTranscriptomeAnti-Bacterial AgentsBacterial ProteinsDaptomycinTeichoic Acids

Identifiers

PMID26883712
PMCPMC4862447
OpenAlexW2275825698

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.